Purpose Antimalarials (AM) may be considered anchor drugs in Systemic Lupus Erythematosus (SLE). Currently, AM treatment is universally recommended for the treatment of SLE, unless contraindicated. Retinopathy is the main concern with prolonged AM exposure. Clinical guidelines suggest baseline screening and then yearly evaluations after the fifth year of therapy, but practice varies widely. We sought to assess AM treatment prevalence and characterize AM discontinuation events in a large well characterized SLE inception cohort. We also explored whether AM discontinuation was associated with differences at the end of follow-up in terms of organ damage, disease activity, and glucocorticoid intake.
Methods 455 consecutive SLE patients (≥4 1982 revised ACR criteria) recruited in the Padua Lupus cohort between 1980 and 2020 were investigated.
Disease activity was assessed by SLEDAI-2K, and damage by the SLICC Damage Index (SDI). A significant damage accrual was defined as SDI major or equal to 2. Use of prednisone at end of follow-up was also reviewed. Retinopathy was defined according to a certified ophthalmologist evaluation employing optical coherence tomography, visual field, electroretinogram, funduscopy as clinically indicated. Categorical variables were analyzed with Chi-square test; when less than 5 events were recorded in a 2x2 table cell, Fisher’s test was used. Clinically relevant known risk factors for retinopathy and factors with a p<0.2 at univariate analysis were entered into a multivariate Cox regression model. The association between damage accrual and AM status was evaluated in a multivariable logistic regression model adjusted for age, disease duration, immunosuppressant use and number of immunosuppressants, and disease activity. Variables were tested for collinearity before running the model.
Results More than 95% of patients were prescribed AMs during the course of SLE (n=435/455). 98/435 (22.5%) discontinued AMs, of which 32 (32.6%) due to retinopathy. Cutaneous reactions (16/98, 16%) and GI intolerance (15/98, 15%) accounted for the majority of the remainder, with a non-trivial subset exhibiting noncompliance (9/98, 9,1%). Clinical characteristics according to AM therapy status are shown in Table 1; organ damage according to the same definitions is shown in Figure 1. Patients with no AM exposure exhibited a severe phenotype, with more neurological involvement, vasculitis, and higher SDI scores (p<0.01). At last follow-up, patients stopping AM therapy were less likely to be in steroid-free remission (p< 0.01). Retinopathy remained associated with higher age at Cox regression (p=0,03). Stopping AMs, due to any reason, remained associated at multivariate analysis with a meaningful damage accrual (p=0,004) and with glucocorticoid use at last follow-up (p<0.001).
Conclusion Antimalarial discontinuation in SLE is associated with higher damage accrual, lower rates of complete remission and with glucocorticoid intake at end of follow-up. Retinopathy accounts for only a third of discontinuations. Every effort should be made by practitioners to enhance antimalarial coverage, retain this class of drugs, and monitor compliance.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.